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1.
BMC Infect Dis ; 24(1): 406, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627642

RESUMO

BACKGROUND: Opportunistic infections (OIs) are common causes of mortality among people living with HIV (PLHIV). We determined prevalence and 30-day mortality due to histoplasmosis, cryptococcosis, and TB in PLHIV with advanced HIV disease (AHD). METHODS: PLHIV 18 years and older, with a CD4 + T-cell count of less than 350 cells/mm3 newly diagnosed with HIV infection or re-engaged in care after being without ART for more than 90 days (Group A). The second group included symptomatic PLHIV regardless of ART status or CD4 + T-cell count (Group B); all followed for 30 days. Detection of Histoplasma Ag (HisAg) in urine was done by enzyme immunoassay (EIA), Cryptococcus antigen (CrAg) was detected in serum and cerebrospinal fluid (CSF) specimens by lateral flow assay (LFA), and lipoarabinomannan (LAM) detection in urine was by LFA (TB LAM) and in sputum by GeneXpert for diagnosis of Mycobacterium infections. RESULTS: From August 2021 to June 2022, 491 PLHIV were enrolled; 482 (98%) had a CD4 + T-cell result, and 381 patients (79%) were classified with AHD according to CD4 + T-cell count (< 200 CD4/mm3). Frequency of an OI was 38% (n = 145/381). Antigen test positivity rate was 16% (72/467) for TB-LAM, 9% (43/464) for HisAg, and 11% (51/484) for CrAg. Twenty-one of 34 (62%) patients receiving CSF CrAg tests were positive, confirming meningitis. Significant differences in 30-day mortality were observed in patients with an OI (16%) vs. no OI (7%) (p = 0.002). Mortality was highest in patients with histoplasmosis (25%), co-infection (22%), cryptococcosis (18% overall; 19% for cryptococcal meningitis), and TB (10%). CONCLUSIONS: TB and fungal OIs, including co-infection, were common in PLHIV in Paraguay and had high associated mortality. Laboratories and health facilities need access to CD4 + T-cell testing and rapid diagnostic assays.


Assuntos
Coinfecção , Criptococose , Infecções por HIV , Histoplasmose , Infecções Oportunistas , Tuberculose , Humanos , Infecções por HIV/epidemiologia , Histoplasmose/diagnóstico , Histoplasmose/epidemiologia , Testes de Diagnóstico Rápido , Paraguai/epidemiologia , Criptococose/complicações , Criptococose/diagnóstico , Criptococose/epidemiologia , Tuberculose/complicações , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Antígenos de Fungos
2.
Andes Pediatr ; 95(1): 77-83, 2024 Feb.
Artigo em Espanhol | MEDLINE | ID: mdl-38587347

RESUMO

Pulmonary cryptococcosis is a lung infection caused by the Cryptococcus yeast. It is rare in pediatrics, especially in immunocompetent children. The diagnosis of pulmonary cryptococcosis can be challenging due to the low specificity of symptoms, low index of suspicion, and limited diagnostic resources. OBJECTIVE: To describe a clinical case of pulmonary cryptococcosis in an immunocompetent adolescent, detailing the diagnostic approach. CLINICAL CASE: A 15-year-old patient, previously healthy, from a rural town, who consulted due to cough and a 1-month rib stitch pain, without fever or associated respiratory difficulty, with two images of condensation in the left lung on the chest x-ray. In the Computed Tomography, the images showed a nodular appearance. Due to suspicion of neoplastic pathology, a Positron Emission Tomography was performed, which showed hypermetabolic nodular lesions. The tomographic characteristics could correspond to fungal or granulomatous involvement. Considering the images and epidemiological risk factors such as rural origin and contact with bird droppings, the possibility of a mycosis was considered. A lung needle biopsy was performed under tomographic guidance. Cryptococcus neoformans was identified in the microbiology laboratory culture. The patient received treatment with itraconazole and fluconazole with good clinical and imaging response after 10 months of therapy and follow-up. CONCLUSION: In immunocompetent patients with a nonspecific clinical presentation, images can guide the diagnosis of pulmonary cryptococcosis, and an etiological search is essential to confirm it. In our case, the CT-guided needle biopsy was of great diagnostic utility.


Assuntos
Criptococose , Cryptococcus neoformans , Pneumopatias Fúngicas , Adolescente , Humanos , Biópsia , Criptococose/diagnóstico por imagem , Criptococose/tratamento farmacológico , Pneumopatias Fúngicas/diagnóstico por imagem , Pneumopatias Fúngicas/tratamento farmacológico , Tomografia Computadorizada por Raios X
3.
BMC Infect Dis ; 24(1): 397, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38609851

RESUMO

BACKGROUND: Cryptococcal osteomyelitis is a rare and potentially serious condition, typically encountered in individuals with compromised immune systems. This case underscores the unusual occurrence of disseminated Cryptococcosis in an immunocompetent person, involving multiple bones and lungs, with Cryptococcus neoformans identified as the causative agent. CASE PRESENTATION: An Indonesian man, previously in good health, presented with a chief complaint of successive multiple bone pain lasting for more one month, without any prior history of trauma. Additionally, he reported a recent onset of fever. On physical examination, tenderness was observed in the left lateral chest wall and right iliac crest. Laboratory findings indicated mildly elevated inflammatory markers. A computed tomography (CT) scan of the chest revealed an ovoid solid nodule in the right lower lung and multifocal osteolytic lesions in the sternum, ribs, and humeral head. A magnetic resonance imaging (MRI) study of the sacrum showed multiple lesions in the bilateral iliac bone and the lower L4 vertebral body. Confirmation of Cryptococcal osteomyelitis involved a fine-needle biopsy and culture, identifying Cryptococcus neoformans in the aspirate. The patient responded positively to targeted antifungal treatments, leading to a gradual improvement in his condition. CONCLUSIONS: This case emphasizes the need to consider Cryptococcus neoformans osteomyelitis in immunocompetent patients with bone pain. A definitive diagnosis involves a fine-needle biopsy for pathology and culture, and prompt initiation of appropriate antifungal treatment has proven effective in preventing mortality.


Assuntos
Criptococose , Cryptococcus neoformans , Osteomielite , Masculino , Humanos , Antifúngicos/uso terapêutico , Criptococose/diagnóstico , Criptococose/tratamento farmacológico , Pulmão , Osteomielite/diagnóstico , Osteomielite/tratamento farmacológico , Dor
4.
Microb Cell Fact ; 23(1): 107, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38609931

RESUMO

Cryptococcus neoformans has been designated as critical fungal pathogens by the World Health Organization, mainly due to limited treatment options and the prevalence of antifungal resistance. Consequently, the utilization of novel antifungal agents is crucial for the effective treatment of C. neoformans infections. This study exposed that the minimum inhibitory concentration (MIC) of isobavachalcone (IBC) against C. neoformans H99 was 8 µg/mL, and IBC dispersed 48-h mature biofilms by affecting cell viability at 16 µg/mL. The antifungal efficacy of IBC was further validated through microscopic observations using specific dyes and in vitro assays, which confirmed the disruption of cell wall/membrane integrity. RNA-Seq analysis was employed to decipher the effect of IBC on the C. neoformans H99 transcriptomic profiles. Real-time quantitative reverse transcription PCR (RT-qPCR) analysis was performed to validate the transcriptomic data and identify the differentially expressed genes. The results showed that IBC exhibited various mechanisms to impede the growth, biofilm formation, and virulence of C. neoformans H99 by modulating multiple dysregulated pathways related to cell wall/membrane, drug resistance, apoptosis, and mitochondrial homeostasis. The transcriptomic findings were corroborated by the antioxidant analyses, antifungal drug sensitivity, molecular docking, capsule, and melanin assays. In vivo antifungal activity analysis demonstrated that IBC extended the lifespan of C. neoformans-infected Caenorhabditis elegans. Overall, the current study unveiled that IBC targeted multiple pathways simultaneously to inhibit growth significantly, biofilm formation, and virulence, as well as to disperse mature biofilms of C. neoformans H99 and induce cell death.


Assuntos
Chalconas , Criptococose , Cryptococcus neoformans , Animais , Cryptococcus neoformans/genética , Antifúngicos/farmacologia , RNA-Seq , Simulação de Acoplamento Molecular , Biofilmes , Caenorhabditis elegans
5.
Front Cell Infect Microbiol ; 14: 1321886, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38558853

RESUMO

Cryptococcosis is a life-threatening invasive fungal infection with significantly increasing mortality worldwide, which is mainly caused by Cryptococcus neoformans and Cryptococcus gattii. These two species complexes have different epidemiological and clinical characteristics, indicating the importance of accurate differential diagnosis. However, the clinically used culture method and cryptococcal capsular antigen detection couldn't achieve the above goals. Herein, we established a novel duplex flap probe-based isothermal assay to identify the Cryptococcus neoformans and Cryptococcus gattii within 1 hour. This assay combined the highly sensitive nucleic acid isothermal amplification and highly specific fluorescence probe method, which could effectively distinguish the sequence differences of the two species complexes using two different fluorescence flap probes in a single reaction system. This novel method showed excellent detection performance with sensitivity (10 copies/µL each) and specificity (100%) compared to traditional culture and sequencing methods. Furthermore, we applied this method to spiked clinical samples, 30 cerebrospinal fluids and 30 bronchoalveolar lavage fluids, which kept good detection performance. This novel rapid duplex flap probe-based isothermal assay is a promising and robust tool for applications in differential diagnosis of the Cryptococcus neoformans and Cryptococcus gattii in clinical settings, especially when clinical suspicion for cryptococcal disease is high and epidemiological studies.


Assuntos
Criptococose , Cryptococcus gattii , Cryptococcus neoformans , Humanos , Cryptococcus neoformans/genética , Cryptococcus gattii/genética , Criptococose/diagnóstico , Criptococose/microbiologia , Antígenos de Fungos , Líquido da Lavagem Broncoalveolar
6.
PeerJ ; 12: e17030, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38487258

RESUMO

Background: Patients with poor prognosis of pulmonary cryptococcosis (PC) are prone to other complications such as meningeal infection, recurrence or even death. Therefore, this study aims to analyze the influencing factors in the poor prognosis of patients with PC, so as to build a predictive nomograph model of poor prognosis of PC, and verify the predictive performance of the model. Methods: This retrospective study included 410 patients (78.1%) with improved prognosis of PC and 115 patients (21.9%) with poor prognosis of PC. The 525 patients with PC were randomly divided into the training set and validation set according to the ratio of 7:3. The Least Absolute Shrinkage and Selection Operator (LASSO) algorithm was used to screen the demographic information, including clinical characteristics, laboratory test indicators, comorbidity and treatment methods of patients, and other independent factors that affect the prognosis of PC. These factors were included in the multivariable logistic regression model to build a predictive nomograph. The receiver operating characteristic curve (ROC), calibration curve and decision curve analysis (DCA) were used to verify the accuracy and application value of the model. Results: It was finally confirmed that psychological symptoms, cytotoxic drugs, white blood cell count, hematocrit, platelet count, CRP, PCT, albumin, and CD4/CD8 were independent predictors of poor prognosis of PC patients. The area under the curve (AUC) of the predictive model for poor prognosis in the training set and validation set were 0.851 (95% CI: 0.818-0.881) and 0.949, respectively. At the same time, calibration curve and DCA results confirmed the excellent performance of the nomogram in predicting poor prognosis of PC. Conclusion: The nomograph model for predicting the poor prognosis of PC constructed in this study has good prediction ability, which is helpful for improving the prognosis of PC and further optimizing the clinical management strategy.


Assuntos
Criptococose , Nomogramas , Humanos , Estudos Retrospectivos , Albuminas , Algoritmos , Criptococose/diagnóstico
7.
mBio ; 15(4): e0307823, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38511961

RESUMO

Cryptococcus neoformans causes lethal meningitis and accounts for approximately 10%-15% of AIDS-associated deaths worldwide. There are major gaps in our understanding of how this fungus invades the mammalian brain. To investigate the dynamics of C. neoformans tissue invasion, we mapped fungal localization and host cell interactions in infected brain, lung, and upper airways using mouse models of systemic and airway infection. To enable this, we developed an in situ imaging pipeline capable of measuring large volumes of tissue while preserving anatomical and cellular information by combining thick tissue sections, tissue clarification, and confocal imaging. We confirm high fungal burden in mouse upper airway after nasal inoculation. Yeast in turbinates were frequently titan cells, with faster kinetics than reported in mouse lungs. Importantly, we observed one instance of fungal cells enmeshed in lamina propria of the upper airways, suggesting penetration of airway mucosa as a possible route of tissue invasion and dissemination to the bloodstream. We extend previous literature positing bloodstream dissemination of C. neoformans, by finding viable fungi in the bloodstream of mice a few days after intranasal infection. As early as 24 h post systemic infection, the majority of C. neoformans cells traversed the blood-brain barrier, and were engulfed or in close proximity to microglia. Our work presents a new method for investigating microbial invasion, establishes that C. neoformans can breach multiple tissue barriers within the first days of infection, and demonstrates microglia as the first cells responding to C. neoformans invasion of the brain.IMPORTANCECryptococcal meningitis causes 10%-15% of AIDS-associated deaths globally. Still, brain-specific immunity to cryptococci is a conundrum. By employing innovative imaging, this study reveals what occurs during the first days of infection in brain and in airways. We found that titan cells predominate in upper airways and that cryptococci breach the upper airway mucosa, which implies that, at least in mice, the upper airways are a site for fungal dissemination. This would signify that mucosal immunity of the upper airway needs to be better understood. Importantly, we also show that microglia, the brain-resident macrophages, are the first responders to infection, and microglia clusters are formed surrounding cryptococci. This study opens the field to detailed molecular investigations on airway immune response, how fungus traverses the blood-brain barrier, how microglia respond to infection, and ultimately how microglia monitor the blood-brain barrier to preserve brain function.


Assuntos
Síndrome de Imunodeficiência Adquirida , Criptococose , Cryptococcus neoformans , Meningite , Camundongos , Animais , Microglia , Criptococose/microbiologia , Encéfalo/microbiologia , Mamíferos
8.
Arch Microbiol ; 206(4): 153, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38472387

RESUMO

3-Bromopyruvate (3BP), known for its potent anticancer properties, also exhibits remarkable efficacy against the pathogenic fungus Cryptococcus neoformans. So far it has been proven that the main fungicidal activity of 3BP is based on ATP depletion and a reduction of intracellular level of glutathione. The presented study includes a broad range of methods to further investigate the mechanistic effects of 3BP on C. neoformans cells. The use of flow cytometry allowed a thorough examination of their survival during 3BP treatment, while observations using electron microscopy made it possible to note the changes in cellular morphology. Utilizing ruthenium red, the study suggests a mitochondrial pathway may initiate programmed cell death in response to 3BP. Analysis of free radical generation and gene expression changes supports this hypothesis. These findings enhance comprehension of 3BP's mechanisms in fungal cells, paving the way for its potential application as a therapeutic agent against cryptococcosis.


Assuntos
Criptococose , Cryptococcus neoformans , Cryptococcus neoformans/metabolismo , Piruvatos/metabolismo , Piruvatos/farmacologia , Piruvatos/uso terapêutico , Criptococose/tratamento farmacológico , Apoptose
9.
Front Immunol ; 15: 1356651, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38469300

RESUMO

Cryptococcus neoformans and C. gattii, the etiologic agents of cryptococcosis, cause over 100,000 deaths worldwide every year, yet no cryptococcal vaccine has progressed to clinical trials. In preclinical studies, mice vaccinated with an attenuated strain of C. neoformans deleted of three cryptococcal chitin deacetylases (Cn-cda1Δ2Δ3Δ) were protected against a lethal challenge with C. neoformans strain KN99. While Cn-cda1Δ2Δ3Δ extended the survival of mice infected with C. gattii strain R265 compared to unvaccinated groups, we were unable to demonstrate fungal clearance as robust as that seen following KN99 challenge. In stark contrast to vaccinated mice challenged with KN99, we also found that R265-challenged mice failed to induce the production of protection-associated cytokines and chemokines in the lungs. To investigate deficiencies in the vaccine response to R265 infection, we developed a KN99-R265 coinfection model. In unvaccinated mice, the strains behaved in a manner which mirrored single infections, wherein only KN99 disseminated to the brain and spleen. We expanded the coinfection model to Cn-cda1Δ2Δ3Δ-vaccinated mice. Fungal burden, cytokine production, and immune cell infiltration in the lungs of vaccinated, coinfected mice were indicative of immune evasion by C. gattii R265 as the presence of R265 neither compromised the immunophenotype established in response to KN99 nor inhibited clearance of KN99. Collectively, these data indicate that R265 does not dampen a protective vaccine response, but rather suggest that R265 remains largely undetected by the immune system.


Assuntos
Coinfecção , Criptococose , Cryptococcus gattii , Cryptococcus neoformans , Vacinas , Camundongos , Animais , Evasão da Resposta Imune
10.
Curr Protoc ; 4(3): e1001, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38456766

RESUMO

Cryptococcus is recognized as one of the emerging fungal pathogens that have major impact on diverse populations worldwide. Because of the high mortality rate and limited antifungal therapy options, there is an urgent need to understand the impact of dynamic processes between fungal pathogens and hosts that influence cryptococcal pathogenesis and disease outcomes. With known common limitations in human studies, experimental murine cryptococcosis models that can recapitulate human disease provide a valuable tool for studying fungal virulence and the host interaction, leading to development of better treatment strategies. Infection with Cryptococcus in mice via intranasal inhalation is mostly used because it is noninvasive and considered to be the most common mode of infection, strongly correlating with cryptococcal disease in humans. The protocols described in this article provide the procedures of establishing a murine model of Cryptococcus infection by intranasal inhalation and assessing the host immune response and disease progression during Cryptococcus infection. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Murine model of pulmonary cryptococcal infection via intranasal inhalation Basic Protocol 2: Assessment of the pulmonary immune response during Cryptococcus infection Support Protocol: Evaluation of pulmonary gene expression by real-time PCR Basic Protocol 3: Enumeration of survival rate and organ fungal burden.


Assuntos
Criptococose , Cryptococcus gattii , Cryptococcus neoformans , Humanos , Animais , Camundongos , Cryptococcus neoformans/genética , Modelos Animais de Doenças , Criptococose/microbiologia , Criptococose/patologia , Pulmão/microbiologia , Pulmão/patologia
11.
Virulence ; 15(1): 2327883, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38465639

RESUMO

Cryptococcus neoformans is an environmental yeast that primarily affects immunocompromised individuals, causing respiratory infections and life-threatening meningoencephalitis. Treatment is complicated by limited antifungal options, with concerns such as adverse effects, dose-limiting toxicity, blood-brain barrier permeability, and resistance development, emphasizing the critical need to optimize and expand current treatment options against invasive cryptococcosis. Galleria mellonella larvae have been introduced as an ethical intermediate for in vivo testing, bridging the gap between in vitro antifungal screening and mouse studies. However, current infection readouts in G. mellonella are indirect, insensitive, or invasive, which hampers the full potential of the model. To address the absence of a reliable non-invasive method for tracking infection, we longitudinally quantified the cryptococcal burden in G. mellonella using bioluminescence imaging (BLI). After infection with firefly luciferase-expressing C. neoformans, the resulting bioluminescence signal was quantitatively validated using colony-forming unit analysis. Longitudinal comparison of BLI to health and survival analysis revealed increased sensitivity of BLI in discriminating cryptococcal burden during early infection. Furthermore, BLI improved the detection of treatment efficacy using first-line antifungals, thereby benchmarking this model for antifungal testing. In conclusion, we introduced BLI as a real-time, quantitative readout of cryptococcal burden in G. mellonella over time, enabling more sensitive and reliable antifungal screening.


Assuntos
Criptococose , Cryptococcus neoformans , Mariposas , Animais , Antifúngicos/uso terapêutico , Criptococose/microbiologia , Larva/microbiologia , Mariposas/microbiologia
12.
J Med Microbiol ; 73(3)2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38530134

RESUMO

Introduction. Cryptococcal biofilms have been associated with persistent infections and antifungal resistance. Therefore, strategies, such as the association of natural compounds and antifungal drugs, have been applied for the prevention of biofilm growth. Moreover, the Caenorhabditis elegans pathogenicity model has been used to investigate the capacity to inhibit the pathogenicity of Cryptococcus neoformans sensu stricto.Hypothesis. Anthraquinones and antifungals are associated with preventing C. neoformans sensu stricto biofilm formation and disrupting these communities. Antraquinones reduced the C. neoformans sensu stricto pathogenicity in the C. elegans model.Aim. This study aimed to evaluate the in vitro interaction between aloe emodin, barbaloin or chrysophanol and itraconazole or amphotericin B against growing and mature biofilms of C. neoformans sensu stricto.Methodology. Compounds and antifungal drugs were added during biofilm formation or after 72 h of growth. Then, the metabolic activity was evaluated by the MTT reduction assay, the biomass by crystal-violet staining and the biofilm morphology by confocal laser scanning microscopy. C. neoformans sensu stricto's pathogenicity was investigated using the nematode C. elegans. Finally, pathogenicity inhibition by aloe emodin, barbarloin and chrysophanol was investigated using this model.Results. Anthraquinone-antifungal combinations affected the development of biofilms with a reduction of over 60 % in metabolic activity and above 50 % in biomass. Aloe emodin and barbaloin increased the anti-biofilm activity of antifungal drugs. Chrysophanol potentiated the effect of itraconazole against C. neoformans sensu stricto biofilms. The C. elegans mortality rate reached 76.7 % after the worms were exposed to C. neoformans sensu stricto for 96 h. Aloe emodin, barbaloin and chrysophanol reduced the C. elegans pathogenicity with mortality rates of 61.12 %, 65 % and 53.34 %, respectively, after the worms were exposed for 96 h to C. neoformans sensu stricto and these compounds at same time.Conclusion. These results highlight the potential activity of anthraquinones to increase the effectiveness of antifungal drugs against cryptococcal biofilms.


Assuntos
Antracenos , Criptococose , Cryptococcus neoformans , Animais , Antifúngicos/farmacologia , Caenorhabditis elegans , Itraconazol , Virulência , Antraquinonas/farmacologia , Biofilmes
13.
Clin Respir J ; 18(3): e13746, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38529683

RESUMO

OBJECTIVES: The aim of this study is to evaluate the diagnostic value of rapid on-site evaluation (ROSE) combined with computed tomography-guided percutaneous needle biopsy (CT-PNB) or radial endobronchial ultrasound-guided transbronchial lung biopsy (EBUS-TBLB) for pulmonary cryptococcosis (PC). METHODS: Clinical data of 33 patients diagnosed with PC at the Third Affiliated Hospital of Soochow University between February 2018 and June 2023 were retrospectively analysed. Patients were divided into the CT-PNB and EBUS-TBLB groups based on the intervention method, and the diagnostic positivity rate and incidence of complications were compared between the two groups. RESULTS: Compared with the final diagnosis, the positive diagnostic rates of ROSE, histopathology and serum CrAg of all patients were 81.8% (27/33), 72.7% (24/33) and 63.6% (21/33), respectively. The average turnaround times of the three methods were 0.1 (0.1-0.2) h, 96.0 (48.0-120.0) h and 7.8 (4.5-13.6) h, respectively (P < 0.001). The coincidence rate between histopathology and ROSE was 84.8% with a kappa value of 0.574. The positive diagnostic rate for PC was significantly higher in the CT-PNB group than in the EBUS-TBLB group (92.9% vs. 57.9%), and the difference was statistically significant (P < 0.05). Combined with the ROSE results, the positive diagnostic rate in the EBUS-TBLB group increased to 84.2% (16/19). CONCLUSION: ROSE has commendable accuracy and timeliness, and CT-PNB offers further advantages in this regard. ROSE enhances the diagnostic efficiency of EBUS-TBLB for PC and is safe and effective.


Assuntos
Criptococose , Neoplasias Pulmonares , Pneumologia , Humanos , Avaliação Rápida no Local , Estudos Retrospectivos , Broncoscopia/métodos , Biópsia Guiada por Imagem/métodos , Criptococose/diagnóstico , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia
14.
Medicine (Baltimore) ; 103(12): e37455, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38518007

RESUMO

RATIONALE: Cryptococcosis presenting as endobronchial obstruction and lung collapse is an extremely rare occurrence. While these patients were treated with antifungal agents, unfortunately, half of them showed a suboptimal response. PATIENT CONCERNS: A 45-year-old immunocompetent male was admitted to the hospital due to a cough, yellow phlegm, and dyspnea persisting for 5 months. Chest computer tomography revealed a mass in the right main bronchus accompanied by right lower lobe atelectasis. DIAGNOSES: Endobronchial cryptococcosis presenting as endobronchial obstruction and lung collapse. INTERVENTIONS: Early rigid bronchoscopic therapy was performed to resect endobronchial obstruction, which combined with antifungal agent. OUTCOMES: The patient recovered well with completely clinical and radiologic resolution at 1 year follow-up. LESSONS: This case provides a good example of successful utilization of the early respiratory interventional therapy combined with antifungal agent in obstructive endobronchial cryptococcosis.


Assuntos
Obstrução das Vias Respiratórias , Broncopatias , Criptococose , Atelectasia Pulmonar , Humanos , Masculino , Pessoa de Meia-Idade , Antifúngicos/uso terapêutico , Criptococose/diagnóstico , Criptococose/tratamento farmacológico , Brônquios/diagnóstico por imagem , Brônquios/microbiologia , Pulmão/microbiologia , Broncopatias/tratamento farmacológico , Broncopatias/complicações , Obstrução das Vias Respiratórias/etiologia
15.
J Med Chem ; 67(6): 4726-4738, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38489247

RESUMO

Cryptococcus neoformans (C. neoformans) and Candida albicans (C. albicans) are classified as the critical priority groups among the pathogenic fungi, highlighting the urgent need for developing more effective antifungal therapies. On the basis of antifungal natural product sampangine, herein, a series of tricyclic oxime and oxime ether derivatives were designed. Among them, compound WZ-2 showed excellent inhibitory activity against C. neoformans (MIC80 = 0.016 µg/mL) and synergized with fluconazole to treat resistant C. albicans (FICI = 0.078). Interestingly, compound WZ-2 effectively inhibited virulence factors (e.g., capsule, biofilm, and yeast-to-hypha morphological transition), suggesting the potential to overcome drug resistance. In a mouse model of cryptococcal meningitis, compound WZ-2 (5 mg/kg) effectively reduced the brain C. neoformans H99 burden. Furthermore, compound WZ-2 alone and its combination with fluconazole also significantly reduced the kidney burden of the drug-resistant strain (0304103) and sensitive strain (SC5314) of C. albicans.


Assuntos
Alcaloides , Candidíase , Criptococose , Cryptococcus neoformans , Compostos Heterocíclicos de 4 ou mais Anéis , Naftiridinas , Animais , Camundongos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Fluconazol/farmacologia , Fluconazol/uso terapêutico , Criptococose/tratamento farmacológico , Criptococose/microbiologia , Candidíase/tratamento farmacológico , Candida albicans , Testes de Sensibilidade Microbiana
16.
Zhonghua Jie He He Hu Xi Za Zhi ; 47(3): 214-221, 2024 Mar 12.
Artigo em Chinês | MEDLINE | ID: mdl-38448170

RESUMO

A 64-year-old female patient was admitted to Beijing Chao-Yang Hospital on February 21, 2023 because of right-sided chest pain for more than 4 years and left-sided chest pain for more than 9 months. She had a past medical history of previous tuberculosis and rheumatoid arthritis. A chest CT in October 2018 revealed multiple pulmonary nodules. A CT-guided biopsy showed no tumors, and adenosine deaminase levels in the pleural effusion were elevated, suggesting a high likelihood of tuberculosis. As a result, anti-tuberculosis treatment was initiated in March 2019. In December 2019, she underwent a right lower lobe resection due to localized hydropneumothorax on the right side. Postoperative pathology unveiled granulomatous inflammation with necrosis. A chest CT in May 2020 showed a significant increase in nodules and cavities. In January 2023, a diagnosis of cryptococcal pneumonia was considered, and she was prescribed oral fluconazole. Finally, the diagnosis of pulmonary rheumatoid nodules was confirmed after a pathological consultation of the postoperative specimen. After one month of treatment with oral prednisone and mycophenolate mofetil, a follow-up chest CT showed improvement. It was recommended that she continue with her current treatment and undergo regular chest CT scans.


Assuntos
Criptococose , Nódulos Pulmonares Múltiplos , Tuberculose , Humanos , Feminino , Pessoa de Meia-Idade , Dor no Peito , Criptococose/diagnóstico , Hospitalização
17.
Washington, D.C.; PAHO; 2024-03-22. (PAHO/UFCSPA/CDE/HT/23-0015).
Não convencional em Inglês | PAHO-IRIS | ID: phr-59381

RESUMO

People living with HIV (PLHIV) with severe advanced disease are at high risk of developing opportunistic infections and may face barriers related to diagnosis and treatment. The objective of this study was to describe insights, experiences and perspectives around the feasibility of implementing a package for the rapid diagnosis of frequent opportunistic infections among patients with advanced HIV, in order to support the development and implementation of HIV care policies. The study was carried out between June 30 and October 30, 2023, comprising two focus groups with health professionals involved in the rapid diagnosis intervention (n=10); four in-depth interviews with health managers dedicated to HIV care policies; and 12 interviews with patients with advanced HIV. The intervention in question was considered relevant for allowing a more timely diagnosis of diseases that are difficult to investigate. Patient compliance was generally collaborative, especially in research hospitals, but more vulnerable patients may require expanded psychosocial support. Among the barriers, delays in results, communication challenges between professionals and patients were highlighted, as well as the lack of alignment in the flow of exam request, collection, results and communication for patients and the extended team. At the management level, the importance of integrating the intervention into the line of care for patients with HIV was highlighted. It is relevant to investigate the issue of social determinants of HIV/AIDS mortality in the future to provide valuable insights into improving prevention and treatment strategies.


Assuntos
Tuberculose , Histoplasmose , Criptococose , HIV , Síndrome de Imunodeficiência Adquirida , Infecções Oportunistas , Política de Saúde , Doenças Transmissíveis , Brasil
18.
BMC Infect Dis ; 24(1): 162, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38321369

RESUMO

BACKGROUND: Pulmonary cryptococcosis (PC) rarely occurs in immunocompetent children. CASE PRESENTATION: A 13-year-old boy was admitted to the First Affiliated Hospital of Ningbo University in February 2023 with complaints of cough and chest pain. Physical examination showed slightly moist rales in the right lung. Chest computed tomography (CT) suggested a lung lesion and cavitation. Blood routine test, lymphocyte subsets, immunoglobulin, and complement tests indicated that the immune system was normal. However, the serum cryptococcal antigen test was positive. Next-generation sequencing revealed Cryptococcus infection. The child was diagnosed with PC and was discharged after treating with fluconazole 400 mg. Four months later, chest CT showed that the lung lesion diminished, and reexamination of serum cryptococcal antigen test turned positive. CONCLUSION: PC should be considered in an immunocompetent child with pulmonary cavities with nonspecific symptoms.


Assuntos
Criptococose , Masculino , Criança , Humanos , Adolescente , Criptococose/diagnóstico , Fluconazol , Pulmão , Tomografia Computadorizada por Raios X , Antígenos de Fungos
19.
Rev Soc Bras Med Trop ; 57: e008002023, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38324809

RESUMO

Previously considered saprobe and non-pathogenic, the fungus Papiliotrema laurentii (formerly known as Cryptococcus laurentii), is rarely associated with human infection. Nevertheless, there has been an increase in reported infections by non-neoformans cryptococci. After a literature search on the Cochrane Library, LILACS, SciELO, MEDLINE, PubMed, and PMC (PubMed Central) databases, we conclude that this is the first case report of fungemia and probable meningitis caused by Papiliotrema laurentii in a previously immunocompetent host with associated COVID-19.


Assuntos
Basidiomycota , COVID-19 , Criptococose , Cryptococcus , Fungemia , Humanos , Fungemia/complicações , Fungemia/diagnóstico , Fungemia/microbiologia , Criptococose/microbiologia , COVID-19/complicações , SARS-CoV-2
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